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Abstract
The enigma of Sizzled, a secreted Frizzled-related protein, has been resolved in a recent study from the De Robertis lab ( [in the January 13 issue of Cell]). Sizzled, although homologous to other Wnt antagonists, does not function as such, nor does it function within a Wnt signaling pathway. Remarkably it functions as an antagonist of BMP signaling, competing with Chordin for binding to its inhibitor a Tolloid-related metalloprotease. This competition protects Chordin from cleavage, thus allowing it to bind and limit BMP signaling.